ES2585110T3 - Derivados de pirimidina como inhibidores de proteína cinasa - Google Patents
Derivados de pirimidina como inhibidores de proteína cinasa Download PDFInfo
- Publication number
- ES2585110T3 ES2585110T3 ES13156251.4T ES13156251T ES2585110T3 ES 2585110 T3 ES2585110 T3 ES 2585110T3 ES 13156251 T ES13156251 T ES 13156251T ES 2585110 T3 ES2585110 T3 ES 2585110T3
- Authority
- ES
- Spain
- Prior art keywords
- positive
- compound
- tetrahydro
- nmr
- pyrimido
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
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- 229940045988 antineoplastic drug protein kinase inhibitors Drugs 0.000 title 1
- 239000003909 protein kinase inhibitor Substances 0.000 title 1
- 229940083082 pyrimidine derivative acting on arteriolar smooth muscle Drugs 0.000 title 1
- 150000003230 pyrimidines Chemical class 0.000 title 1
- 150000001875 compounds Chemical class 0.000 abstract description 21
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 24
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 18
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 18
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 15
- 238000005160 1H NMR spectroscopy Methods 0.000 description 13
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 10
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 7
- 239000007787 solid Substances 0.000 description 7
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 6
- FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 6
- 238000000034 method Methods 0.000 description 5
- CQIUZHAQYHXKRY-VIFPVBQESA-N (2s)-2-amino-3-phenylpropanal Chemical compound O=C[C@@H](N)CC1=CC=CC=C1 CQIUZHAQYHXKRY-VIFPVBQESA-N 0.000 description 4
- OKKJLVBELUTLKV-MZCSYVLQSA-N Deuterated methanol Chemical compound [2H]OC([2H])([2H])[2H] OKKJLVBELUTLKV-MZCSYVLQSA-N 0.000 description 4
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 4
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 4
- IJOOHPMOJXWVHK-UHFFFAOYSA-N chlorotrimethylsilane Chemical compound C[Si](C)(C)Cl IJOOHPMOJXWVHK-UHFFFAOYSA-N 0.000 description 4
- -1 9-cyclopentyl-6-oxo-6,7,8,9-tetrahydro-5H-pyrimido [4,5-b] [1,4] diazepin-2-ylamino Chemical group 0.000 description 3
- 206010028980 Neoplasm Diseases 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 239000002253 acid Substances 0.000 description 3
- 150000001412 amines Chemical class 0.000 description 3
- 201000011510 cancer Diseases 0.000 description 3
- 238000006243 chemical reaction Methods 0.000 description 3
- 239000003795 chemical substances by application Substances 0.000 description 3
- PAFZNILMFXTMIY-UHFFFAOYSA-N cyclohexylamine Chemical compound NC1CCCCC1 PAFZNILMFXTMIY-UHFFFAOYSA-N 0.000 description 3
- 235000019439 ethyl acetate Nutrition 0.000 description 3
- 239000000203 mixture Substances 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 2
- 125000000217 alkyl group Chemical group 0.000 description 2
- 125000005605 benzo group Chemical group 0.000 description 2
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid group Chemical group C(C1=CC=CC=C1)(=O)O WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 2
- 238000000132 electrospray ionisation Methods 0.000 description 2
- 238000005984 hydrogenation reaction Methods 0.000 description 2
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 2
- 235000019341 magnesium sulphate Nutrition 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 229910052708 sodium Inorganic materials 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- 235000009518 sodium iodide Nutrition 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 238000011282 treatment Methods 0.000 description 2
- FQUYSHZXSKYCSY-UHFFFAOYSA-N 1,4-diazepane Chemical compound C1CNCCNC1 FQUYSHZXSKYCSY-UHFFFAOYSA-N 0.000 description 1
- MEKOFIRRDATTAG-UHFFFAOYSA-N 2,2,5,8-tetramethyl-3,4-dihydrochromen-6-ol Chemical compound C1CC(C)(C)OC2=C1C(C)=C(O)C=C2C MEKOFIRRDATTAG-UHFFFAOYSA-N 0.000 description 1
- KRQUFUKTQHISJB-YYADALCUSA-N 2-[(E)-N-[2-(4-chlorophenoxy)propoxy]-C-propylcarbonimidoyl]-3-hydroxy-5-(thian-3-yl)cyclohex-2-en-1-one Chemical compound CCC\C(=N/OCC(C)OC1=CC=C(Cl)C=C1)C1=C(O)CC(CC1=O)C1CCCSC1 KRQUFUKTQHISJB-YYADALCUSA-N 0.000 description 1
- SKDJWBCTSQLYAZ-UHFFFAOYSA-N 2-chloro-9-cyclopentyl-7,7-dimethyl-5,8-dihydropyrimido[4,5-b][1,4]diazepin-6-one Chemical compound C12=NC(Cl)=NC=C2NC(=O)C(C)(C)CN1C1CCCC1 SKDJWBCTSQLYAZ-UHFFFAOYSA-N 0.000 description 1
- SXIGGRXSMJJARA-UHFFFAOYSA-N 2-chloro-9-phenyl-7,8-dihydro-5h-pyrimido[4,5-b][1,4]diazepin-6-one Chemical compound C12=NC(Cl)=NC=C2NC(=O)CCN1C1=CC=CC=C1 SXIGGRXSMJJARA-UHFFFAOYSA-N 0.000 description 1
- FPZJXYUHFHCHAK-UHFFFAOYSA-N 3-methoxy-4-[(5-methyl-6-oxo-9-phenyl-7,8-dihydropyrimido[4,5-b][1,4]diazepin-2-yl)amino]-n-(1-methylpiperidin-4-yl)benzamide Chemical compound COC1=CC(C(=O)NC2CCN(C)CC2)=CC=C1NC(N=C12)=NC=C1N(C)C(=O)CCN2C1=CC=CC=C1 FPZJXYUHFHCHAK-UHFFFAOYSA-N 0.000 description 1
- CKKCYWXFAHYHMM-UHFFFAOYSA-N 4-[(5-ethyl-6-oxo-9-pentan-3-yl-7,8-dihydropyrimido[4,5-b][1,4]diazepin-2-yl)amino]-3-methoxy-n-(1-methylpiperidin-4-yl)benzamide Chemical compound N1=C2N(C(CC)CC)CCC(=O)N(CC)C2=CN=C1NC(C(=C1)OC)=CC=C1C(=O)NC1CCN(C)CC1 CKKCYWXFAHYHMM-UHFFFAOYSA-N 0.000 description 1
- ZMQXLAPSJVDSRK-UHFFFAOYSA-N 4-[(9-benzyl-5-methyl-6-oxo-7,8-dihydropyrimido[4,5-b][1,4]diazepin-2-yl)amino]-3-methoxy-n-(1-methylpiperidin-4-yl)benzamide Chemical compound COC1=CC(C(=O)NC2CCN(C)CC2)=CC=C1NC(N=C12)=NC=C1N(C)C(=O)CCN2CC1=CC=CC=C1 ZMQXLAPSJVDSRK-UHFFFAOYSA-N 0.000 description 1
- ZXTIFFIFGCEFPS-UHFFFAOYSA-N 9-benzyl-2-chloro-7,8-dihydro-5h-pyrimido[4,5-b][1,4]diazepin-6-one Chemical compound C12=NC(Cl)=NC=C2NC(=O)CCN1CC1=CC=CC=C1 ZXTIFFIFGCEFPS-UHFFFAOYSA-N 0.000 description 1
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 1
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Natural products C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 1
- 238000005481 NMR spectroscopy Methods 0.000 description 1
- 102100031463 Serine/threonine-protein kinase PLK1 Human genes 0.000 description 1
- 108010022394 Threonine synthase Proteins 0.000 description 1
- 102000005497 Thymidylate Synthase Human genes 0.000 description 1
- 229910021529 ammonia Inorganic materials 0.000 description 1
- 235000019270 ammonium chloride Nutrition 0.000 description 1
- 239000000908 ammonium hydroxide Substances 0.000 description 1
- 239000008346 aqueous phase Substances 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- PUJDIJCNWFYVJX-UHFFFAOYSA-N benzyl carbamate Chemical class NC(=O)OCC1=CC=CC=C1 PUJDIJCNWFYVJX-UHFFFAOYSA-N 0.000 description 1
- VHXBIBFCJISKFA-UHFFFAOYSA-N benzyl n-(4-oxocyclohexyl)carbamate Chemical compound C=1C=CC=CC=1COC(=O)NC1CCC(=O)CC1 VHXBIBFCJISKFA-UHFFFAOYSA-N 0.000 description 1
- KUYRDAWXIBUVCA-UHFFFAOYSA-N benzyl n-cyclohexylcarbamate Chemical compound C=1C=CC=CC=1COC(=O)NC1CCCCC1 KUYRDAWXIBUVCA-UHFFFAOYSA-N 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 230000008878 coupling Effects 0.000 description 1
- 238000010168 coupling process Methods 0.000 description 1
- 238000005859 coupling reaction Methods 0.000 description 1
- AUELWJRRASQDKI-UHFFFAOYSA-N cyclohexyl carbamate Chemical compound NC(=O)OC1CCCCC1 AUELWJRRASQDKI-UHFFFAOYSA-N 0.000 description 1
- 231100000433 cytotoxic Toxicity 0.000 description 1
- 230000001472 cytotoxic effect Effects 0.000 description 1
- 239000002274 desiccant Substances 0.000 description 1
- 238000010828 elution Methods 0.000 description 1
- WNXYZAACJCTSAS-UHFFFAOYSA-N ethyl 1-[[(5-amino-2-chloropyrimidin-4-yl)-cyclopentylamino]methyl]cyclopropane-1-carboxylate Chemical compound C1CCCC1N(C=1C(=CN=C(Cl)N=1)N)CC1(C(=O)OCC)CC1 WNXYZAACJCTSAS-UHFFFAOYSA-N 0.000 description 1
- CSUOMZQWAMSEKH-UHFFFAOYSA-N ethyl 3-[(5-amino-2-chloropyrimidin-4-yl)-cyclopentylamino]-2,2-dimethylpropanoate Chemical compound N=1C(Cl)=NC=C(N)C=1N(CC(C)(C)C(=O)OCC)C1CCCC1 CSUOMZQWAMSEKH-UHFFFAOYSA-N 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 150000003840 hydrochlorides Chemical class 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 239000005457 ice water Substances 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 239000000543 intermediate Substances 0.000 description 1
- 239000013067 intermediate product Substances 0.000 description 1
- 208000032839 leukemia Diseases 0.000 description 1
- 238000001819 mass spectrum Methods 0.000 description 1
- VHMBLVOMCMPHAR-UHFFFAOYSA-N methyl 3-[(2-chloro-5-nitropyrimidin-4-yl)-(oxan-4-yl)amino]propanoate Chemical compound N=1C(Cl)=NC=C([N+]([O-])=O)C=1N(CCC(=O)OC)C1CCOCC1 VHMBLVOMCMPHAR-UHFFFAOYSA-N 0.000 description 1
- HICWQDAYOSASCW-UHFFFAOYSA-N methyl 3-[(2-chloro-5-nitropyrimidin-4-yl)-cyclohexylamino]butanoate Chemical compound N=1C(Cl)=NC=C([N+]([O-])=O)C=1N(C(C)CC(=O)OC)C1CCCCC1 HICWQDAYOSASCW-UHFFFAOYSA-N 0.000 description 1
- CWFFTYOPCNSPSR-UHFFFAOYSA-N methyl 3-[(2-chloro-5-nitropyrimidin-4-yl)-cyclohexylamino]propanoate Chemical compound N=1C(Cl)=NC=C([N+]([O-])=O)C=1N(CCC(=O)OC)C1CCCCC1 CWFFTYOPCNSPSR-UHFFFAOYSA-N 0.000 description 1
- YAMIMLRPPHTJPC-UHFFFAOYSA-N methyl 3-[(2-chloro-5-nitropyrimidin-4-yl)-cyclopentylamino]-2-methylpropanoate Chemical compound N=1C(Cl)=NC=C([N+]([O-])=O)C=1N(CC(C)C(=O)OC)C1CCCC1 YAMIMLRPPHTJPC-UHFFFAOYSA-N 0.000 description 1
- ZQDIWHPICJKOIC-UHFFFAOYSA-N methyl 3-[(2-chloro-5-nitropyrimidin-4-yl)-cyclopentylamino]-4-methylpentanoate Chemical compound N=1C(Cl)=NC=C([N+]([O-])=O)C=1N(C(C(C)C)CC(=O)OC)C1CCCC1 ZQDIWHPICJKOIC-UHFFFAOYSA-N 0.000 description 1
- CJSCUSXWHCWQHI-UHFFFAOYSA-N methyl 3-[(2-chloro-5-nitropyrimidin-4-yl)-pentan-3-ylamino]propanoate Chemical compound COC(=O)CCN(C(CC)CC)C1=NC(Cl)=NC=C1[N+]([O-])=O CJSCUSXWHCWQHI-UHFFFAOYSA-N 0.000 description 1
- 150000002780 morpholines Chemical class 0.000 description 1
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 238000011275 oncology therapy Methods 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- 108010056274 polo-like kinase 1 Proteins 0.000 description 1
- 238000004007 reversed phase HPLC Methods 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- CZDYPVPMEAXLPK-UHFFFAOYSA-N tetramethylsilane Chemical compound C[Si](C)(C)C CZDYPVPMEAXLPK-UHFFFAOYSA-N 0.000 description 1
- 239000003643 water by type Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/06—Antiasthmatics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/08—Bronchodilators
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/12—Drugs for disorders of the urinary system of the kidneys
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/06—Antipsoriatics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/02—Antineoplastic agents specific for leukemia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D453/00—Heterocyclic compounds containing quinuclidine or iso-quinuclidine ring systems, e.g. quinine alkaloids
- C07D453/02—Heterocyclic compounds containing quinuclidine or iso-quinuclidine ring systems, e.g. quinine alkaloids containing not further condensed quinuclidine ring systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/10—Spiro-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D519/00—Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups C07D453/00 or C07D455/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/55—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
- A61K31/551—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole having two nitrogen atoms, e.g. dilazep
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
Landscapes
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Pulmonology (AREA)
- Epidemiology (AREA)
- Rheumatology (AREA)
- Urology & Nephrology (AREA)
- Pain & Pain Management (AREA)
- Oncology (AREA)
- Immunology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Physical Education & Sports Medicine (AREA)
- Dermatology (AREA)
- Hematology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB0719038A GB0719038D0 (en) | 2007-09-28 | 2007-09-28 | Compound |
| GB0719038 | 2007-09-28 | ||
| GB0806844 | 2008-04-15 | ||
| GB0806844A GB0806844D0 (en) | 2008-04-15 | 2008-04-15 | Compound |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ES2585110T3 true ES2585110T3 (es) | 2016-10-03 |
Family
ID=40199600
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
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| MX2010001677A (es) | 2007-08-15 | 2010-03-11 | Vertex Pharma | Derivados de 4-(9-(3,3-difluorociclopentil)-5,7,7-trimetil-6-oxo-6 ,7,8,9-tetrahidro-5h-pirimido[4,5-b][1,4]diazepin-2-ilamino)-3-me toxibenzamida como inhibidores de las proteinas cinasas humanas plk1 a plk4 para el tratamiento de enfermedades proli |
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| NZ601453A (en) | 2008-06-23 | 2014-05-30 | Vertex Pharma | Protein kinase inhibitors |
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| RU2012116525A (ru) * | 2009-09-25 | 2013-10-27 | Вертекс Фармасьютикалз Инкорпорейтед | Способы получения перемидиновых производных, пригодных в качестве ингибиторов протеинкиназ |
| BR112012006639A2 (pt) | 2009-09-25 | 2015-09-08 | Vertex Pharma | métodos para preparar derivados de pirimidina úteis como inibidores de protéina quinase |
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| CN103492381A (zh) | 2010-12-16 | 2014-01-01 | 沃泰克斯药物股份有限公司 | 流感病毒复制的抑制剂 |
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| JP2017504653A (ja) | 2014-01-31 | 2017-02-09 | ダナ−ファーバー キャンサー インスティテュート， インコーポレイテッド | ジアミノピリミジンベンゼンスルホン誘導体およびその使用 |
| KR101517414B1 (ko) * | 2014-04-24 | 2015-05-04 | 고려대학교 산학협력단 | 염증성 질환의 예방 또는 치료용 약학 조성물 |
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| JP6704416B2 (ja) | 2015-05-13 | 2020-06-03 | バーテックス ファーマシューティカルズ インコーポレイテッドＶｅｒｔｅｘ Ｐｈａｒｍａｃｅｕｔｉｃａｌｓ Ｉｎｃｏｒｐｏｒａｔｅｄ | インフルエンザウイルスの複製の阻害剤を調製する方法 |
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| JP2018526424A (ja) | 2015-09-11 | 2018-09-13 | ダナ−ファーバー キャンサー インスティテュート， インコーポレイテッド | アセトアミドチエノトリアゾロジアゼピンおよびこれらの使用 |
| US10738016B2 (en) | 2015-10-13 | 2020-08-11 | H. Lee Moffitt Cancer Center And Research Institute, Inc. | BRD4-kinase inhibitors as cancer therapeutics |
| JP7385356B2 (ja) | 2015-11-25 | 2023-11-22 | ダナ－ファーバー キャンサー インスティテュート， インコーポレイテッド | 二価ブロモドメインインヒビターおよびそれらの使用 |
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| KR20080095902A (ko) * | 2006-02-14 | 2008-10-29 | 버텍스 파마슈티칼스 인코포레이티드 | 단백질 키나제의 억제제로서 유용한 디하이드로디아제핀 |
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| WO2010083505A1 (en) | 2009-01-19 | 2010-07-22 | The Trustees Of The University Of Pennsylvania | Method of treating cancer using a survivin inhibitor |
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| CN101878216A (zh) | 2010-11-03 |
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| US20110046093A1 (en) | 2011-02-24 |
| CN101878216B (zh) | 2013-07-10 |
| ES2457394T3 (es) | 2014-04-25 |
| EP2205603A1 (en) | 2010-07-14 |
| EP2610256B1 (en) | 2016-04-27 |
| JP2010540509A (ja) | 2010-12-24 |
| HK1146042A1 (en) | 2011-05-13 |
| CA2700979A1 (en) | 2009-04-02 |
| PL2610256T3 (pl) | 2016-11-30 |
| JP5410432B2 (ja) | 2014-02-05 |
| WO2009040556A1 (en) | 2009-04-02 |
| US9493471B2 (en) | 2016-11-15 |
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